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      Front-Line Maintenance Therapy in Advanced Ovarian Cancer—Current Advances and Perspectives

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          Abstract

          Ovarian tumor is the gynecological cancer associated with the highest mortality. Most diseases are diagnosed at an advanced stage, which impairs the chances of prolonged complete remission. The standard front-line treatment of advanced stages combines surgery in an expert center with platinum-based chemotherapy. Most patients experience a relapse in the years following the initial treatment. During the last decade, anti-angiogenic agents used in the maintenance setting improved progression free survival (PFS) over chemotherapy alone. More recently, PARP inhibitors demonstrated substantial efficacy, mainly in patients with germinal or somatic BRCA mutations or other homologous recombination deficiencies (HRD), all involved in double strand DNA Damage Repair (DDR). Other therapeutic paradigms are currently being explored, including combinations of immune-checkpoints inhibitors, chemotherapy, bevacizumab and PARP inhibitors. In addition to these clinical advances, molecular characterization of the tumors and their correlations with drugs efficacy are needed to better understand which patient will benefit the most from the various treatments available to date.

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          Most cited references79

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.

            BRCA1 and BRCA2 are important for DNA double-strand break repair by homologous recombination, and mutations in these genes predispose to breast and other cancers. Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in base excision repair, a key pathway in the repair of DNA single-strand breaks. We show here that BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis. This seems to be because the inhibition of PARP leads to the persistence of DNA lesions normally repaired by homologous recombination. These results illustrate how different pathways cooperate to repair damage, and suggest that the targeted inhibition of particular DNA repair pathways may allow the design of specific and less toxic therapies for cancer.
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              Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer

              Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib in relapsed disease has been well established, but the benefit of olaparib as maintenance therapy in newly diagnosed disease is uncertain.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                25 August 2020
                September 2020
                : 12
                : 9
                : 2414
                Affiliations
                [1 ]Oncology Department, Hôpital Lyon Sud, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL) and Université de Lyon, 69310 Lyon, France; christophe.sajous@ 123456chu-lyon.fr (C.S.); julien.peron@ 123456chu-lyon.fr (J.P.); benoit.you@ 123456chu-lyon.fr (B.Y.); gilles.freyer@ 123456univ-lyon1.fr (G.F.)
                [2 ]Departement of Surgical Oncology, Centre Hospitalier Lyon-Sud, 69310 Lyon, France; olivier.glehen@ 123456chu-lyon.fr (O.G.); naoual.bakrin@ 123456chu-lyon.fr (N.B.)
                [3 ]EA CICLY, Lyon 1 University, 69310 Lyon, France; witold.gertych@ 123456chu-lyon.fr
                [4 ]Department of Gynecological Surgery, Centre Hospitalier Lyon-Sud, 69310 Lyon, France
                [5 ]Biochemistry and Molecular Biology Department, Hopital Lyon Sud, Hospices Civils de Lyon, 69310 Lyon, France; jonathan.lopez@ 123456chu-lyon.fr
                Author notes
                Author information
                https://orcid.org/0000-0002-9696-7050
                https://orcid.org/0000-0003-3768-2378
                Article
                cancers-12-02414
                10.3390/cancers12092414
                7564452
                32854393
                dba634ca-7c62-4130-9235-2862d2c13a09
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 July 2020
                : 21 August 2020
                Categories
                Review

                ovarian cancer,front-line maintenance therapy,parp inhibitors,anti-angiogenics,immunotherapy,brca 1/2,homologous recombination deficiency

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